Techniques for Avoiding Unexpected Problems in LC and GC Analysis

Significance of the Topic

High‐quality chromatography relies on effective sample preparation to prevent matrix‐induced instrument contamination, unpredictable retention shifts, peak distortion, and ion suppression. Robust cleanup enhances detection sensitivity, method reliability, and instrument longevity in LC, GC, and MS analyses.

Objectives and Overview of the Study

This white paper surveys practical strategies for eliminating physical and chemical matrix effects in liquid and gas chromatography. It reviews rapid approaches (dilute-and-shoot), physical and chemical filtration, liquid-liquid and supported liquid extraction, QuEChERS, solid phase extraction (SPE), and solid phase microextraction (SPME).

Methodology and Instrumentation

• Dilution and direct injection for fast screening.
• Syringe filters and filter vials for particulate removal.
• Captiva EMR-Lipid, EMR-HCF, EMR-GPF, Carbon S sorbents for lipid and pigment cleanup.
• Supported liquid extraction (Chem Elut S) for LLE‐like performance without emulsions.
• QuEChERS salt extraction with dispersive SPE cleanup kits.
• Polymeric SPE phases (Bond Elut Plexa, HLB, PFAS WAX) for broad or selective analyte capture.
• SPME fibers and Arrows for solvent-free trace analyte enrichment.
• Analytical platforms: UHPLC/HPLC with ESI-MS and MS/MS, GC and GC/MS(/MS), LC-Q-TOF, LC-QQQ, DAD detectors, automated 96-well plate manifolds.

Main Results and Discussion

• Captiva EMR-Lipid removed >99% phospholipids, reducing RSD from >25% to <3%, improving peak shape and lowering detection limits.
• Carbon S sorbent achieved efficient pigment removal in plant-derived foods while preserving planar analytes, outperforming traditional graphitized carbon black.
• Chem Elut S SLE cartridges delivered 87–119% recoveries for aromatic amines with RSDs under 8%, eliminating emulsions and simplifying workflow.
• Pass-through EMR with Carbon S saved 15–30% processing time compared to dSPE, streamlining QuEChERS workflows.
• Bond Elut PFAS WAX cartridges met EPA Method 533 and ISO 21675:2019 requirements with minimal blank artifacts for PFAS monitoring.

Benefits and Practical Applications

• Protects columns and inlets from fouling, reducing downtime and maintenance costs.
• Enhances method robustness and reproducibility across diverse matrices (biological fluids, foods, environmental samples).
• Enables higher throughput with rapid pass-through and 96-well formats.
• Supports regulatory compliance for pesticides, drugs of abuse, lipids, PFAS, and multiclass residue analysis.

Used Instrumentation

• Agilent LC systems with ESI-MS/MS and Q-TOF detectors
• Agilent GC and GC/MS(/MS) platforms
• Automated SPE and filtration manifolds, 96-well plate centrifuges
• SPME autosamplers for fiber and Arrow techniques

Future Trends and Possibilities

The field is evolving toward integrated inline cleanup modules, hybrid sorbents combining multimodal selectivity, greener extraction solvents, automated and digitalized sample preparation workflows, and expansion of solvent-free SPME methods. Advances in affinity and molecularly imprinted phases and coupling with ion mobility and high-resolution MS will drive next-generation matrix removal and trace analysis.

Conclusion

Optimal sample cleanup tailored to matrix characteristics is essential for reliable LC/GC analysis. The reviewed techniques—from simple filtration to advanced SPE and SPME—offer pathways to improved data quality, lower operating costs, and greater throughput. Matching the correct method to analytical goals ensures robust performance across applications.

References

• EPA Method 533 and EPA Method 1633 (draft)
• ISO 21675:2019 Water Quality – PFAS Determination
• Application Notes: 5994-2830EN, 5994-1783EN, 5994-4960EN, 5994-5667EN